The purpose of the present proposal is to strengthen and expand the research programs on metabolic regulation in neoplasia presently carried out in the Laboratory for Experimental Oncology of Indiana University School of Medicine. The individual research projects include investigations on (1) regulation of gene expression linked with control of cellular proliferation in mammalian cells; (2) control of purine biosynthesis and catabolism; (3) regulation of pentose phosphate metabolism; (4) control of gene expression in liver tumors; (5) control mechanisms of DNA metabolism in normal and neoplastic proliferation; (6) experimental chemotherapy in tissue culture and in solid tumors; (7) control of enzyme turnover through regulation of degradation and regulation of ornithine metabolism; (8) regulation of PRPP amidotransferase by drugs and hormones in normal and cancer cells; (9) control of template activity and study of morphology of plasma membrane; (10) regulation of synthesis and degradation of lipids and serine metabolism; (11) karyotype and chromosome banding pattern in somatic cell hybrids in slow and rapidly growing hepatomas; (12) role of cyclic nucleotides in neoplasia with special relevance to plasma cell membrane compartmentation; (13) properties of purified PRPP amidotransferase from normal and neoplastic cells; (14) regulation of uridylate metabolism in normal, differentiating and cancer cells. These investigations are targeted to elucidate the control of gene expression as metabolic regulation is linked to differentiation in normal and neoplastic growth processes. An essential part of the proposal includes a number of projects involving collaboration among various investigators within and also outside the Laboratory for Experimental Oncology. The proposed Core Grant would obtain these objectives, to expand and strengthen our research program on metabolic regulation in neoplasia, by supporting the central facilities for research, to be shared by investigators involved in this program, and by providing adequate salaries for the young scientists. The central theme of this proposal is the application of the concepts and techniques of modern experimental oncology, biochemical pharmacology and metabolic regulation to the study of neoplastic cells.